Patients suffering from central nervous system disorders (CNS) such as spinal cord injury, multiple sclerosis, and Parkinson’s disease often develop neurogenic detrusor overactivity (NDO), which currently lacks universally effective therapy. Neurogenic bladder dysfunction caused by spinal cord injury is a serious threat to the well-being of patients also has many consequences. Renal damage, stones, urinary incontinence, urinary tract infection, and poor quality of life are some of these consequences. Cerebrolysin (CL) is a neuropeptide preparation and manufactured in a sophisticated, fully controlled biotechnological process which it contains amino acids and important neuropeptides. CL is used in the CNS injuries like traumatic brain injury, dementia, stroke, and multiple sclerosis by inducing neuroprotection which possible mechanisms of that are the help to neural survivor, neuroplasticity, and neurogenesis. Also, in spinal cord injured animals, CL treatment showed neuroprotection property so that its effect was time and dose-dependent. So, neurogenic bladder dysfunction as a neurological disorder in the spinal cord could be a treatment target using CL. The aim of this study was to investigate the therapeutic effect of CL in SCI-induced neurogenic bladder dysfunction in rats. For this purpose, we applied three dosages of CL in the acute and chronic phase of SCI and analyzed immunohistochemical and western blot findings.

A total of sixty female Wistar rats randomly divided into 10 groups (n=6). All of the rats were separated into 10 groups (n=6 in per group) as follows: Control, sham-operated, SCI animals received saline normal daily for 1 week or 4 weeks, three acute treatment groups including SCI animals received 1, 2.5 and 5 ml/kg CL for 1 week, three chronic treatment groups including SCI animals received 1, 2.5 and 5 ml/kg CL for 4 weeks. Drug intervention began just after complete transection at the T9-T10 level of rat spinal cord. In acute groups, intraperitoneal injection of cerebrolysin performed for 7 days (1 week) and in chronic groups continued for 28 days (4 weeks). At the end of drug intervention, spinal cord and bladder tissue were harvested for immunohistological and western blotting process.

Immunohistochemical evaluation of GAP43 (growth associated protein 43), a marker of axonal sprouting, in spinal cord tissue showed that in the chronic phase, there were a significant difference among sham and SCI+saline (4 weeks) groups (p<0.01), but in acute group there were no significant difference among sham and SCI+saline (1week) groups (p =0.064). Also, a significant difference was observed between intervention and SCI+saline groups in all three groups received 1, 2.5, and 5 ml/kg cerebrolysin (p<0.001), in the both of acute and chronic phase. Immunoblotting analysis of ERK1/2 expression in spinal cord showed that in the both of acute and chronic phase, ERK1/2 expression in the spinal cord in groups received cerebrolysin in 2.5, and 5 ml/kg in compare to SCI+saline groups significantly increased (p<0.01),(p<0.001), respectively. Immunoblotting analysis of ERK1/2 expression in bladder showed that in both acute and chronic phase there was a significant difference between intervention and SCI+saline groups and among all intervention groups (p<0.001). No significant difference was observed among SCI-saline and sham groups in both acute (p=0.95) and chronic phase (p=0.97).

A dose-dependent elevation in GAP-43 expression was observed in treatment groups. Cerebrolysin by amplification of ERK 1/2 signaling pathway cause neurogenesis and differentiation. So that, systemic injection of cerebrolysin resulted in significant increase in ERK1/2 expression in both spinal cord and bladder tissues. This elevation was significant in rat spinal cord which received 2.5 and 5 ml/kg cerebrolysin, in both of the acute and chronic phases, but significant increase in ERK1/2 expression in rats bladder that received all three dosages of 1, 2.5, and 5 ml/kg cerebrolysin was observed. But 2.5 seems to be the more safe based number of survived rats.

Our results show that Cerebrolysin as a mixed growth factor, have a potential role in the improvement of neural pathways and neurogenesis in the spinal cord and bladder. This new finding of the effect of Cerebrolysin in the improvement of neurogenic bladder disorder could be useful in SCI patients.